Emergent eukaryotic directional sensing via receptor degradation and diffusion

• 成果类型: Article
• 署名作者: Goetz, Andrew; Dixit, Purushottam
• 署名单位: Yale University; Yale University; Yale University; Yale University
• 刊物名称: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• ISSN/ISSBN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.2516077122
• 发表日期: 2025-12-23
• 页码: e2516077122
• 关键词: directional sensing; reaction diffusion; integral feedback; PERFECT ADAPTATION; LOCAL-EXCITATION; chemotaxis; endocytosis; cells; MODEL; DICTYOSTELIUM; COMMUNICATION; cooperativity; amplification

摘要

Directional sensing enables eukaryotic cells to detect spatial gradients of extracellular ligands, allowing them to orient and migrate within complex environments. Prevalent models explain this computation through a circuit where signaling species with distinct diffusion constants act incoherently on a downstream readout. Here, we propose a fundamentally different mechanism of directional sensing based on simple receptor-level processes. Our model integrates three ubiquitous receptor processes-lateral diffusion, basal ligand-independent activation, and active receptor degradation, THAT together synergize to generate robust directional sensing. In the absence of diffusion, active receptor degradation and basal activity implement an integral feedback that adapts active receptor levels to a ligand-independent set point while depleting receptors in relatively ligand-rich regions. Diffusion then redistributes receptors from regions of relatively low ligand exposure to regions with higher ligand exposure. This creates a spatial mismatch between activity and feedback that drives asymmetric receptor activity relative to the set point. The model predicts an optimal diffusion constant that maximizes polarization, reveals that receptors can encode relative rather than absolute ligand concentrations, and identifies the optimal basal activity that maximizes the signal-to-noise ratio in stochastic regimes. A survey of kinetic parameters across receptor families suggests that this diffusion-degradation synergy constitutes a broadly applicable, receptor-level mechanism for directional sensing.